The development of cardiac hypertrophy in response to a sustained stress is a fundamental property of the heart. Recent studies suggest that the intrinsic contractile properties of hypertrophied cardiac muscle vary according to the nature of the inciting stimulus, being decreased in some forms of pressure overload and remaining normal in volume overload. However, the most common form of pressure overload in man, systemic hypertension, has not been studied experimentally. In addition, it is not known whether chronic cardiac hypertrophy and the attendant alterations in contractile function are completely reversible if the imposed stress is removed. Furthermore, the role of lysosomal degradative enzymes in the development and regression of cardiac hypertrophy of various etiologies is unknown. Therefore, we propose to study experimental cardiac hypertrophy in rats and rabbits induced by aortic banding, spontaneous hypertension, A-V fistulae, and chronic hypoxia. Changes in mechanical performance of the heart muscle during induction of hypertrophy and during regression of hypertrophy (after the initial stimulus to hypertrophy is removed) will be monitored; simultaneously changes in the cardiac activities and localization of cathepsin D and other hydrolytic enzymes will be measured. In all instances, comparable measurements of normal control animals will be made for all mechanical and biochemical parameters. Such studies should provide an experimental basis for the better understanding and treatment of cardiac hypertrophy in man. BIBLIOGRAPHIC REFERENCES: Wildenthal, K., and Mueller, EA: Lysosomal enzymes in the development and regression of myocardial hypertrophy induced by systemic hypertension. J. Molec. Cell. Cardiol. 9:121-130, 1977. Mueller, EA, Griffin, WST, and Wildenthal, K: Isoproterenol-induced cardiopathy: changes in cardiac enzymes and protection by methylprednisolone, J. Molec. Cell. Cardiol. (June, 1977), in Press.